Composite xenohybrid bovine bone-derived scaffold as bone substitute for the treatment of tibial plateau fractures

Introduction: Tibial plateau fractures represent a common challenge for orthopaedic surgeons, sometimes representing complex cases to manage, where augmentation using bone grafts is required for stabilisation. Autologous iliac bone graft (AIBG) is the current gold standard for bone grafting. In order to overcome limitations related to the procedure, alternative strategies, like allogenic and xenogeneic bone substitutes have been investigated. Here, within the framework of an observational clinical study, we report clinical and radiological outcomes of patients treated for tibial plateau fractures with a composite xenohybrid bone graft, aiming at assessing clinical and radiological outcomes. Materials and Methods: We performed a cohort retrospective study of patients treated for tibial plateau fractures from May 2017 to January 2018. Thirty-four patients, i.e. 100% of those having received the bone graft under investigation for tibial plateaux fracture treatment, met the inclusion criteria and were enrolled in the study. Patients were assessed at 2 weeks, and then at a 1-, 3-, and 6-months, and 1-year follow-up. At each evaluation patients filled a visual analogue scale (VAS) for the level of pain during the day life activities and underwent physical exam and anteroposterior and lateral projection radiographs of the knee. At 1 year the Tegner Lysholm Scoring Scale, International Knee Document Committee 2000 (IKDC 2000), and Short Form (36) Health Survey (SF-36) were administered. Results: At 1-year, mean VAS decreased from 6.33 \ub1 1.40 to 1 \ub1 0.79 (P < 0.0001); Tegner Lysholm Scoring Scale was 89 \ub1 4.10 and mean IKDC 2000 was 78.67 \ub1 3.31. No infections, neurovascular complications or adverse effects related to implants werereported during the clinical exams at follow-up. Mean ROM was 124 \ub1 6\ub0. Radiographs did not show defects of consolidation or progressive post-surgical subsidence and demonstrated a good grade of integration of the implant. Conclusions: Clinical and radiological outcomes, and scores of questionnaires, were good. The xenograft has demonstrated to be a safe biomaterial, with satisfactory mechanical and biological performances in the mid-term period. It also showed a high grade of osteointegration and remodelling

Design and clinical application of injectable hydrogels for musculoskeletal therapy

Musculoskeletal defects are an enormous healthcare burden and source of pain and disability for individuals. With an ageing population, the proportion living with these medical indications will increase. Simultaneously, there is pressure on healthcare providers to source efficient solutions, which are cheaper and less invasive than conventional technology. This has led to an increased research focus on hydrogels as highly biocompatible biomaterials that can be delivered through minimally invasive procedures. This review will discuss how hydrogels can be designed for clinical translation, particularly in the context of the new European Medical Device Regulation (MDR). We will then do a deep dive into the clinically used hydrogel solutions that have been commercially approved or have undergone clinical trials in Europe or the US. We will discuss the therapeutic mechanism and limitations of these products. Due to the vast application areas of hydrogels, this work focuses only on treatments of cartilage, bone, and the nucleus pulposus. Lastly, the main steps towards clinical translation of hydrogels as medical devices are outlined. We suggest a framework for how academics can assist small and medium MedTech enterprises conducting the initial clinical investigation and Post-Market Clinical Follow-up (PMCF) required in the MDR. It is evident that the successful translation of hydrogels is governed by acquiring high-quality pre-clinical and clinical data confirming the device mechanism of action and safety

Biomaterial-mediated factor delivery for spinal cord injury treatment

Spinal cord injury (SCI) is an injurious process that begins with immediate physical damage to the spinal cord and associated tissues during an acute traumatic event. However, the tissue damage expands in both intensity and volume in the subsequent subacute phase. At this stage, numerous events exacerbate the pathological condition, and therein lies the main cause of post-traumatic neural degeneration, which then ends with the chronic phase. In recent years, therapeutic interventions addressing different neurodegenerative mechanisms have been proposed, but have met with limited success when translated into clinical settings. The underlying reasons for this are that the pathogenesis of SCI is a continued multifactorial disease, and the treatment of only one factor is not sufficient to curb neural degeneration and resulting paralysis. Recent advances have led to the development of biomaterials aiming to promote in situ combinatorial strategies using drugs/biomolecules to achieve a maximized multitarget approach. This review provides an overview of single and combinatorial regenerative-factor-based treatments as well as potential delivery options to treat SCIs

Hydrogel-nanoparticles composite system for controlled drug delivery

Biodegradable poly(ethylene glycol)-block-poly(-lactic acid) (PEG-b-PLA) nanoparticles (NPs) were prepared by nanoprecipitation with controlled dimension and with different electric charges, as monitored by dynamic light scattering (DLS). Then NPs were loaded within hydrogels (HG) developed for biomedical applications in the central nervous system, with different pore sizes (30 and 90 nm). The characteristics of the resulting composite hydrogel-NPs system were firstly studied in terms of ability to control the release of small steric hindrance drug mimetic. Then, diffusion-controlled release of different charged NPs from different entangled hydrogels was studied in vitro and correlated with NPs electric charges and hydrogel mean mesh size. These studies showed different trends, that depend on NPs superficial charge and HG mesh size. Release experiments and diffusion studies, then rationalized by mathematical modeling, allowed us to build different drug delivery devices that can satisfy different medical needs

A Methodologic Approach for the Selection of Bio-Resorbable Polymers in the Development of Medical Devices: The Case of Poly(L-lactide-co-epsilon-caprolactone)

In the last decades bioresorbable and biodegradable polymers have gained a very good reputation both in research and in industry thanks to their unique characteristics. They are able to ensure high performance and biocompatibility, at the same time avoiding post-healing surgical interventions for device removal. In the medical device industry, it is widely known that product formulation and manufacturing need to follow specific procedures in order to ensure both the proper mechanical properties and desired degradation profile. Moreover, the sterilization method is crucial and its impact on physical properties is generally underestimated. In this work we focused our attention on the effect of different terminal sterilization methods on two commercially available poly(l-lactide-co-ε-caprolactone) with equivalent chemical composition (70% PLA and 30% PCL) and relatively similar initial molecular weights, but different chain arrangements and crystallinity. Results obtained show that crystallinity plays a key role in helping preserve the narrow distribution of chains and, as a consequence, defined physical properties. These statements can be used as guidelines for a better choice of the most adequate biodegradable polymers in the production of resorbable medical devices